Anyone who lives with more than one member of Felis catus knows that our beloved felines love to smell each other’s anal…
When a headline in the Washington Post dubbed COVID “A Plague of the Elderly,” I cringed, envisioning Logan’s Run, the sci-fi classic in which people past a certain age voluntarily die. The film came out in 1976, the year I graduated college.
That would make me, well, elderly.
Yes, older folks are over-represented among those who get very sick or die from COVID, with “nearly 9 out of 10 deaths now in people 65 or older,” WaPo reminds us. That is striking for an age group that makes up only 16 percent of the population. But while media reports trumpet the damning statistics, few delve into the biology behind the elevated risk: it could be that our shorter chromosomes hamper the immune response.
The WaPo article, like others, states the obvious:
“The vulnerability of older people to viruses is neither surprising nor new. The more we age, the more we accumulate scars from previous illness and chronic conditions that put us at higher risk of severe illness.”
Yes, a 75-year-old with COPD is less likely to survive COVID pneumonia than a 75-year-old with healthy lungs. And developing COPD is more likely after decades of exposure to irritants. But number of years by itself may be a surrogate for some other factor.
Might the culprit be telomeres, the tips of chromosomes? They shrink as time passes, like candles burning down.
The “E” Word
Many media reports that link advanced age and COVID severity use the E word. But definitions of the exact precipice into official decrepitude vary.
The United Nations equates elderly with age 60. For Merriam Webster, it’s 65, with a helpful list of synonyms: doddering, over-the-hill, and retired.
A study of use of ‘elderly’ in 20 clinical practice guidelines for pharmacotherapy pharmacotherapy (drug prescribing) from 2014 identified 65 as the key age, but pointed out that rationale “was seldom provided” in guidelines, suggesting that the cutoff is ageist. Instead, clinical practice guidelines and prescribing decisions should “be less based on chronological age, focusing more on establishing a direct link between an individual patient’s characteristics and the pharmacology of their prescribed medication.” In other words, individuality matters.
A report from August 2022 in the Journal of Social Issues put a COVID spin on the discussion: “Is Protecting Older Adults from COVID-19 Ageism?”
The investigators questioned older adults in the UK and Colombia, and concluded that the “undifferentiated way in which especially the role of age as a risk factor was discussed, and the inclusion of all people above the age of 65 into one homogeneous risk group, often neglected … the diversity of older people and their characteristics and thus drew criticism for fueling ageism in society.”
I learned the importance of language in referring to older individuals in grad school. I’d just begun my writing career and had profiled a Nobel prize-winning zoology professor, describing him as “puttering around the lab.” I’ve never forgotten his rage, and today, the word elderly has a similar effect on me.
Telomeres and Shrinkage
The aspect of aging that may be most relevant in COVID severity is the length of the telomeres, the ends of our 46 chromosomes. Each telomere consists of repeats of the DNA sequence TTAGGG, a 6-letter word we share with all other vertebrates. (See this post for details).
At each cell division (mitosis), 50 to 150 of the endmost DNA bases fall off each telomere, slowly shaving the chromosomes. At a certain point of the shrinkage, after about 50 divisions, mitosis halts, as if adhering to a cellular clock. Cancer happens if the clock fails and cell division goes unchecked, in addition to other changes.
Eggs and sperm are exceptions in that their telomeres normally stay long. The gametes use an enzyme, telomerase, which builds their chromosome tips, like adding beads to a necklace. In other cell types, telomerase isn’t made and chromosome tips shrink in sync to the cell division clock.
Telomere shortening is exquisitely sensitive to environmental stimuli. It speeds with chronic stress, obesity, too little exercise, high blood sugar, inflammation, and exposure to toxins or radiation. In addition, thirteen types of extremely rare “short telomere syndromes” result from mutations that whittle down the chromosomes too fast, countering the cell division needed for growth, development, and healing. Organs fail, especially those with normally high rates of cell turnover.
Telomeres, T Cells, and COVID
The COVID connection to telomeres is straightforward: the cells of older individuals have shorter telomeres because more time has passed, and longer telomeres are required for a robust T cell response to viral infection.
T cells stimulate B cells to produce antibodies. Both cell types are white blood cells called lymphocytes.
The levels of T cells are normally low, but rev up very fast in the wake of the initial (innate) part of the immune response. So T cells signal B cells and antibodies pour into the bloodstream.
In COVID, the T cell supply can’t keep up. Antibodies wane. Symptoms worsen.
Clinicians recognized early on that hospitalized COVID patients tended to have too few T cells (called T cell lymphopenia), and the T cells had short telomeres – a double whammy. So after an initial rush of antibodies, the T cells that signal B cells run out, and antibody levels plummet. T cell lymphopenia in COVID patients was not only more common among the more severely stricken, but among the older patients. Were short telomeres to blame?
Abraham Aviv from the Center of Human Development and Aging at New Jersey Medical School, Rutgers, explained the telomere-T cell link as a “bullwhip-like effect” in Lancet Healthy Longevity
“As T-cell production is telomere-length dependent and telomeres shorten with age, older adults are at higher risk of a T-cell shortfall when contracting SARS-CoV-2 than are younger adults. The immune systems of these individuals might also generate an inadequate T-cell response to anti-SARS-CoV-2 vaccination.”
In addition, a T cell contingent that can contain most replicating viruses can’t stand up to SARS-CoV-2. When this happens, action shifts back to the innate (initial) immune response, triggering the flood of damaging proteins of a “cytokine storm” that directly killed many people
To what degree does size really matter for telomeres in protecting against severe COVID? Probably not very much – which is good, because it’s beyond our control.
But of course direct-to-consumer “telomere health DNA tests” promise to “track your cellular age based on your telomere length” so that you can “improve it,” which entails pricy supplement packages to help in the quest for biological youth. (See Telomere Testing: Science or Snake Oil? .) But let’s get back to science.
Dr. Aviv, with James Anderson and colleagues from the University of Washington, used publicly available data on COVID-19 mortality to develop a model that tracks T cell numbers through the life span, published in The Lancet eBioMedicine.
The investigators found that age 50 is around when enough T cells have stunted chromosomes that immunity may begin to fall because they can’t reproduce fast enough. But the researchers also point out that telomere length is an inherited trait – that is, some younger people naturally have short telomeres. They may be among those who develop severe COVID but do not have obvious risk factors.
Alas there’s not much we can do about our chromosome tips.
“Depending on your parents and very little on how you live, your longevity or, as our paper claims, your response to COVID-19, is a function of who you were when you were born,” Anderson said in a news release. He suggested that telomere length information could identify people at lower risk of severe COVID, enabling a more personalized allocation of resources, such as booster shots.
According to my ancient age of 68, my telomeres may be short. But does it count that I exercise at least 90 minutes a day and follow a low-carb, mostly vegetarian diet with intermittent fasting? And I’ve survived cancer twice. In evaluating my risk of severe COVID, I’ll stick to these controllable risk factors, along with common-sense public health measures like vaccination and masking.